Reproduction, Fertility and Development Reproduction, Fertility and Development Society
Vertebrate reproductive science and technology
RESEARCH ARTICLE

Angiogenesis and oxidative stress-related gene variants in recurrent pregnancy loss

Marcela Felix Fortis A * , Lucas Rosa Fraga A B C G * , Juliano André Boquett A B * , Thayne Woycinck Kowalski A , Caroline Gross Dutra A , Rozana Oliveira Gonçalves D , Fernanda Sales Luiz Vianna A B C E , Lavinia Schüler-Faccini A B C and Maria Teresa Vieira Sanseverino A B C F G
+ Author Affiliations
- Author Affiliations

A Postgraduate Program in Genetics and Molecular Biology, Federal University of Rio Grande do Sul (UFRGS), Porto Alegre, 91501-970, Brazil.

B National Institute of Population Medical Genetics (INaGeMP), Porto Alegre, 91501-970, Brazil.

C National System for Information on Teratogenic Agents (SIAT), Medical Genetics Service, Hospital de Clínicas de Porto Alegre, Porto Alegre, 90035- 903, Brazil.

D Obstetrics, Gynaecology and Human Reproduction Department, Federal University of Bahia, Salvador, 40110-100, Brazil.

E Genomic Medicine Laboratory, Hospital de Clínicas de Porto Alegre, Porto Alegre, 90035- 903, Brazil.

F School of Medicine, Pontifical Catholic University of Rio Grande do Sul, Porto Alegre, 90610-000, Brazil.

G Corresponding authors. Emails: msanseverino@hcpa.edu.br; lrf.fraga@gmail.com

Reproduction, Fertility and Development - https://doi.org/10.1071/RD17117
Submitted: 24 March 2017  Accepted: 23 July 2017   Published online: 22 August 2017

Abstract

Recurrent pregnancy loss (RPL) affects ~3–5% of couples attempting to conceive and in around 50% of cases the aetiology remains unknown. Adequate vascularisation and placental circulation are indispensable for the development of a normal pregnancy. Prostaglandin-endoperoxide synthase 2 (PTGS2), vascular endothelial growth factor (VEGF) and the nitric oxide (NO) systems play important roles in reproductive physiology, participating in several steps including implantation and apoptosis of trophoblast cells. In this study we evaluated genetic polymorphisms in the inducible nitric oxide synthase (NOS2), PTGS2 and VEGFA genes as susceptibility factors for RPL. A case-control study was conducted in 149 women having two or more miscarriages and 208 controls. Allele and genotype distributions of the polymorphisms studied in the two groups were not statistically different. However, the dominant model showed that the presence of variant T (TT/GT) of rs2779249 (-1290G > T) of NOS2 was significantly associated with RPL (OR = 1.58, CI 95% = 1.03–2.44; P = 0.037). The increased risk remained significant when adjusted for number of pregnancies, alcohol consumption and ethnicity (OR = 1.92, CI95% = 1.18–3.11; P = 0.008). These results suggest that the variant genotypes of the functional polymorphism rs2779249 in the NOS2 promoter are a potential risk for RPL, possibly due to oxidative stress mechanisms.

Additional keywords: genetics, infertility, miscarriage, repeated miscarriage.


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